Cross-presentation
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The term '''cross-presentation''' denotes the ability of certain [[Antigen presenting cell|antigen-presenting cells]] to take up, process and present extracellular antigens with [[MHC class I]] molecules to [[CD8 T cell]]s (cytotoxic T cells). '''Cross-priming''' describes the stimulation of [[cytotoxic]] CD8<sup>+</sup> T cells by this process<ref>{{cite journal|url=http://www.nature.com/ni/journal/v7/n4/full/ni0406-363.html|title=Cross-priming|last=Bevan|first=Michael J.|journal=Nature Immunology|publisher=Nature Publishing Group|volume=7|pp=363–365|doi=10.1038/ni0406-363|year=2006|pages=363}}</ref>. This process is necessary for immunity against most tumors and against viruses that do not infect [[antigen-presenting cell]]s.<ref name="Heath">Heath WR, Carbone FR. 2001. Cross-presentation in viral immunity and self-tolerance. Nat Rev Immunol 1: 126-34</ref><ref>Rock KL. 1996. A new foreign policy: MHC class I molecules monitor the outside world. Immunol. Today 17: 131-7</ref>
It is also required for induction of cytotoxic immunity by [[vaccination]] with protein antigens, for example in [[tumor vaccination]].<ref>Melief CJ. 2003. Mini-review: Regulation of cytotoxic T lymphocyte responses by dendritic cells: peaceful coexistence of cross-priming and direct priming? Eur J Immunol 33: 2645-54</ref>
===History===
The first evidence of cross-presentation was reported 1976 by Michael J. Bevan after injection of cells carrying [[alloantigen]]s into experimental animals. This resulted in CD8 T cell responses that were induced by antigen-presenting cells of the recipient, implying that these must have taken up and processed the injected cells. This observation was termed “cross-priming”.<ref>Bevan MJ. 1976. Cross-priming for a secondary cytotoxic response to minor H antigens with H-2 congenic cells which do not cross-react in the cytotoxic assay. J. Exp. Med. 143: 1283-8</ref>
Later, there had been much controversy about cross-presentation, which now is believed to have been due to particularities and limitations of some experimental systems used.<ref>Wolkers MC, Brouwenstijn N, Bakker AH, Toebes M, Schumacher TN. 2004. Antigen bias in T cell cross-priming. Science 304: 1314-7</ref>
===Relevance for immunity===
Cross-presentation has been shown to play a role in the immune defense against many [[virus|viruses]] ([[Herpesvirus]], [[Influenzavirus]], [[CMV]], [[Epstein-Barr virus|EBV]], [[SIV]], [[Papillomavirus]],..), [[bacteria]] (Listeria, Salmonella, E.coli,…) and [[tumor]]s (Brain, pancreas, melanoma, leukemia,..).<ref>Huang AY, Golumbek P, Ahmadzadeh M, Jaffee E, Pardoll D, Levitsky H. 1994. Role of bone marrow-derived cells in presenting MHC class I-restricted tumor antigens. Science 264: 961-5</ref><ref>Sigal LJ, Crotty S, Andino R, Rock KL. 1999. Cytotoxic T-cell immunity to virus-infected non-haematopoietic cells requires presentation of exogenous antigen. Nature 398: 77-80</ref>
Cross-priming avoids viral immune evasion strategies, such as suppression of [[antigen-processing]]. Consequently, immune responses against viruses that are able to do so, such as herpes viruses, are largely dependent on cross-presentation.
===Relevance for immune tolerance===
Also self antigens (=autoantigens) are cross-presented, resulting in the elimination of autoreactive CD8 T cells. This mechanism to maintain self tolerance has been termed [[cross-tolerance]].<ref>Kurts C, H Kosaka, FR Carbone, JFAP Miller und WR Heath. 1997. Exogenous class I-restricted cross-presentation of self antigens can lead to deletion of autoreactive CD8+ T cells. J Exp Med 186: 239-245</ref>
===Cell biology===
[[Antigen presenting cell|Antigen-presenting cells]] capable of cross-presentation are primarily [[dendritic cell]]s,<ref>den Haan JM, Lehar SM, Bevan MJ. 2000. CD8(+) but not CD8(-) dendritic cells cross-prime cytotoxic T cells in vivo. J Exp Med 192: 1685-96.</ref><ref>Kurts C, Cannarile M, Klebba I, Brocker T. 2001. Dendritic cells are sufficient to cross-present self-antigens to CD8 T cells in vivo. J Immunol 166: 1439-42.</ref> but also [[macrophage]]s, [[B lymphocyte]]s and [[liver sinusoidal endothelial cells]] have been shown to be able to do so. The intracellular mechanisms of cross-presentation are still unclear, but seem to involve specialized subcellular compartments bearing characteristics of both the [[endoplasmic reticulum]] and the [[endosome]].<ref name="Guermonprez">Guermonprez P, Saveanu L, Kleijmeer M, Davoust J, Van Endert P, Amigorena S. 2003. ER-phagosome fusion defines an MHC class I cross-presentation compartment in dendritic cells. Nature 425: 397-402</ref><ref>Burgdorf S, Kautz A, Böhnert V, Knolle PA, Kurts C. 2007. Distinct antigen uptake and intracellular routing mechanisms in CD4 and CD8 T cell activation. Science, 316: 612-6</ref>
Endocytosed proteins are transported out of this compartment into the [[cytoplasm]] by unknown mechanisms. There they are processed by the [proteasome] into peptides, which are transported by the [[TAP transporter]] into the [[endoplasmic reticulum]] <ref>Cresswell P, Bangia N, Dick T, Diedrich G. 1999. The nature of the MHC class I peptide loading complex. Immunol Rev 172: 21-8</ref><ref name="Guermonprez"> </ref>, or back into the same endosomes <ref>Burgdorf S, Schölz C, Kautz A, Tampé R, Kurts C. 2008. Spatial and mechanistic separation of cross-presentation and endogenous antigen presentation. Nature Immunol, 9: 558-566.</ref>, where they associate with [[MHC class I]] molecules.
Finally, [[MHC class I]] - peptide complexes are transported to the cell surface, where they can be detected by specific [[CD8 T cell]]s.
== References ==
{{Reflist|2}}
==External links==
* {{MeshName|Cross-Presentation}}
[[Category:Immune system]]